Anil Vachani, M.D. is a member of the Pulmonary, Allergy, and Critical Care Division at the University of Pennsylvania School of Medicine and is a faculty-fellow in the Department of Biostatistics and Epidemiology. The career development component of the award proposed herein includes a preceptorship with Dr. Timothy Rebbeck, Director of Cancer Epidemology at Penn, and advanced coursework in molecular epidemiology. Additional training will be obtained in laboratory techniques necessary for the conduct of well designed molecular epidemiologic studies. This program of didactic and applied instruction will extend Dr. Vachani's training, will be directly applicable to timely completion of his research proposal, and will provide him with the necessary foundation to become an independent investigator in the molecular epidemiology of lung cancer. The goal of the proposed research is to evaluate the role of candidate genetic polymorphisms in the determination of outcomes among patients with lung cancer. Lung cancer is the most common worldwide cause of major cancer incidence and mortality. At present, the ability to predict outcome in patients with surgically resected tumors is limited. Although surgical therapy may be curative, a number of variables including mechanisms related to the immune system may influence the risk of recurrence and survival in patients with resected lung cancer. The hypothesis underlying Dr. Vachani's project is that higher levels of immune tolerance and escape play a key role in the outcome of NSCLC. More specifically, we will test the association of genetic variation in immunosuppressive genes with tumor characteristics and outcomes in patients with NSCLC. Gene-gene interactions and higher order interactions will also be evaluated. Results from this project may provide valuable insight into immune mechanisms involved in lung cancer progression and allow for the identification of patients that may benefit from adjuvant therapy, particularly novel immunotherapeutic strategies.